The goals of this project are to test the hypothesis that the development of pathologic pulmonary Th2 cytokine patterns in susceptible animals is due to dysregulated IL-12 responses. The investigator has developed an inbred murine model of allergen-induced airway hyperresponsiveness in which susceptible A/J mice develop antigen-dependent airway hyperreactivity, pulmonary eosinophilic inflammation and elevated IgE levels, concomitant with and dependent upon increases in lung levels of Th2 cytokines. In contrast, resistant C3H/HeJ mice fail to develop airway hyperreactivity, elevated IgE levels, and pulmonary expression of Th2 cytokines after antigen exposure. Preliminary studies demonstrate that differences in IL-12 production in response to allergen exposure likely explains the differential susceptibility of these two strains for the development of allergic airway responses. The investigators will: 1. Further characterize the differential production of IL-12 by A/J and C3H mice, by comparing the production of the functional IL-12 heterodimer (p70) and its two subunits in vitro and in vivo before and after sensitization and challenge with allergens. 2. Determine the role of CD40-CD40L interactions in this differential production of IL-12, by examining the production of IL-12 and the development of allergic airway responses in A/J and C3H mice pretreated with antibodies which block the interaction of CD40 with CD40L. 3. Characterize the influence of cytokines which negatively (IL-4, IL-10) or positively (IFN-g) modulate the production or function of IL-12, by blocking the activity of these cytokines with specific antibodies and examining the resulting production of IL-12 as well as the development of allergic airway responses in both strains of mice.